US3899521A - Complex compounds of aspartic acid with a rare earth metal and zinc - Google Patents
Complex compounds of aspartic acid with a rare earth metal and zinc Download PDFInfo
- Publication number
- US3899521A US3899521A US425060A US42506073A US3899521A US 3899521 A US3899521 A US 3899521A US 425060 A US425060 A US 425060A US 42506073 A US42506073 A US 42506073A US 3899521 A US3899521 A US 3899521A
- Authority
- US
- United States
- Prior art keywords
- zinc
- rare earth
- aspartic acid
- complex
- complex compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 28
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 title claims abstract description 19
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 229910052725 zinc Inorganic materials 0.000 title claims abstract description 18
- 239000011701 zinc Substances 0.000 title claims abstract description 18
- 235000003704 aspartic acid Nutrition 0.000 title claims abstract description 17
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 title claims abstract description 17
- 229910052761 rare earth metal Inorganic materials 0.000 title claims description 17
- 150000002910 rare earth metals Chemical class 0.000 title claims description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 9
- 229910052684 Cerium Inorganic materials 0.000 claims description 8
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 claims description 8
- 229910052777 Praseodymium Inorganic materials 0.000 claims description 7
- PUDIUYLPXJFUGB-UHFFFAOYSA-N praseodymium atom Chemical compound [Pr] PUDIUYLPXJFUGB-UHFFFAOYSA-N 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 5
- 150000003863 ammonium salts Chemical class 0.000 claims description 5
- 239000003054 catalyst Substances 0.000 claims description 5
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 239000002244 precipitate Substances 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 230000001376 precipitating effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 4
- 210000004369 blood Anatomy 0.000 abstract description 4
- 239000003795 chemical substances by application Substances 0.000 abstract description 4
- 210000002700 urine Anatomy 0.000 abstract description 4
- 230000000881 depressing effect Effects 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 229960005261 aspartic acid Drugs 0.000 description 14
- QLHSZVGLSUHUOI-UHFFFAOYSA-N 3,5,6-trihydroxy-2-phenylchromen-4-one Chemical class OC=1C(=O)C2=C(O)C(O)=CC=C2OC=1C1=CC=CC=C1 QLHSZVGLSUHUOI-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- GHLITDDQOMIBFS-UHFFFAOYSA-H cerium(3+);tricarbonate Chemical compound [Ce+3].[Ce+3].[O-]C([O-])=O.[O-]C([O-])=O.[O-]C([O-])=O GHLITDDQOMIBFS-UHFFFAOYSA-H 0.000 description 2
- 230000009918 complex formation Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- RMNCNUNUQBLASX-UHFFFAOYSA-N 2-aminoacetic acid;copper Chemical compound [Cu].NCC(O)=O RMNCNUNUQBLASX-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 108010009736 Protein Hydrolysates Proteins 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- -1 ammonium ions Chemical class 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F3/00—Compounds containing elements of Groups 2 or 12 of the Periodic Table
- C07F3/003—Compounds containing elements of Groups 2 or 12 of the Periodic Table without C-Metal linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
Definitions
- the present invention relates to complex compounds of aspartic acid with trivalent rare earths and zinc. It
- the preferred rare earth is cerium or praseodymium; the preferred aspartic acid is l-aspartic acid. It is assumed that in the compounds according to the invention, the acidic hydrogen of aspartic acid is substituted by the metal and that a complex formation occurs between the amino group and the rare earth.
- the invention also relates to preparations which contain or consist of one or several of the described compounds as effective agents.
- the invention also relates to a process for making the compounds according to the invention which comprises the following steps:
- amino nitrogen of aspartic acid is converted into an ammonium salt.
- this salt is then added the double salt of the trivalent rare earth and zinc by complex formation, with sodium peroxide added as a catalyst.
- the addition compound is precipitated with sodium hydroxide solution and crystallized by the addition of 77 percent alcohol.
- the starting material aspartic acid
- HCl e.g. HCl
- ammonium salt is formed (NI-I being intermediately formed from the amino nitrogen).
- the double salts of trivalent rare earth and zinc are added to the acidic hydrolysate, while heating in the presence of the catalyst sodium peroxide.
- the complexes formed in analogy to the preparation of glycine-copper are precipitated in the cold at the isoelectric point in the neutral range with sodium hydroxide solution, and subsequently washed with 77 percent ethanol, and dried.
- EXAMPLE 1 532.4 g of l-aspartic acid in 500 cc of distilled water and 600 cc of 37 percent HCl were hydrolysed with simultaneous conversion of the amino nitrogen into an ammonium salt. Thereafter, 550.37 g cerium carbonate and 161.44 g zinc sulfate were added, and the mixture heated to 40C, after addition of 0.1 g sodium peroxide as catalyst.
- the so obtained solution was cooled to 30C after filtration from impurities in the cerium carbonate, if any; then 15 cc of 20 percent sodium hydroxide solution were added at room temperature.
- the precipitate which formed was separated by filtration and washed with 77 percent alcohol. Washing was repeated three times.
- the residue obtained was dried at 40C in an oven; it is the cerium/zinc/aspartate complex.
- the yield amounted to about 850 g, the crystalline mass having a melting point of 243.5C and a molecular weight of 994.21.
- EXAMPLE 2 The process was carried out as described in Example 1. However, instead of using cerium, praseodymium was used while the starting material was again 1- aspartic acid.
- a method of preparing a complex compound of aspartic acid with a rare earth and zinc which comprises the steps of converting the amino nitrogen of aspartic acid into an ammonium salt;
- step 2 is carried out with the carbonate of cerium or praseodymium and the sulfate of zinc.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
Complex compounds of aspartic acid with trivalent rare earths and zinc, and medical preparations consisting of or containing said compounds as effective agents in depressing the level of sugar in blood and urine. The invention also relates to a method of making the compounds.
Description
Uite States tent [1 1 Evers [4 1 Aug. 12, 1975 t COMPLEX COMPOUNDS OF ASPARTIC ACID WITH A RARE EARTH METAL AND ZINC [76] Inventor: Walter Ever-s, Siemensstrasse 4,
2080 Pinneberg, Germany [22] Filed: Dec. 14, 1973 [21] Appl. No.: 425,060
[52] US. Cl 260/429.2; 424/289 [51] Int. Cl. C07F 3/06; CO7F 5/00 [58] Field of Search 260/429.2
[56] References Cited OTHER PUBLICATIONS Dreyer et al., Chem. Abs., Vol. 69, 100l4lq (1968).
Primary Examiner-Leland A. Sebastian Attorney, Agent, or Firm-A1lison C. Collard [5 7] ABSTRACT 6 Claims, N0 Drawings COMPLEX COMPOUNDS OF ASPARTIC ACID WITH A RARE EARTH METAL AND ZINC The present invention relates to complex compounds of aspartic acid with trivalent rare earths and zinc. It
also relates to medical preparations containing the complex compounds as efiective ingredients, and to a method of making the same.
It is known to influence the level of sugar in blood or urine by oral administration of sulfonyl derivatives and products based upon biguanides, as well as similar medication with substances obtained by total extraction of vegetables, e.g., bean peels. It is further known from German Pat. No. 936,592 that similar effects may be obtained by compounds of rare earths with parts of plants containing glycosides of trihydroxyflavones.
It was found quite unexpectedly that complex compounds of aspartic acid with trivalent rare earths and zinc are particularly effective in depressing the level of blood sugar and urine sugar.
It is therefore an object of the present invention to prepare complex compounds of aspartic acid with trivalent rare earths and zinc, and to use them in medical preparations as a depressant for sugar in blood and urine. The preferred rare earth is cerium or praseodymium; the preferred aspartic acid is l-aspartic acid. It is assumed that in the compounds according to the invention, the acidic hydrogen of aspartic acid is substituted by the metal and that a complex formation occurs between the amino group and the rare earth. The invention also relates to preparations which contain or consist of one or several of the described compounds as effective agents.
It was further found that these complex compounds are capable of highly increasing the effects of the abovementioned trihydroxyflavones. According to one embodiment of the invention, medical preparations are claimed which contain as effective agents, one or more complexes of trihydroxyflavone with a trivalent rare earth.
The invention also relates to a process for making the compounds according to the invention which comprises the following steps:
The amino nitrogen of aspartic acid is converted into an ammonium salt. To this salt is then added the double salt of the trivalent rare earth and zinc by complex formation, with sodium peroxide added as a catalyst. In further steps, the addition compound is precipitated with sodium hydroxide solution and crystallized by the addition of 77 percent alcohol.
More particularly, the process may be carried out as follows:
The starting material, aspartic acid, is hydrolysed by addition of e.g. HCl, whereby in a manner known per se, the ammonium salt is formed (NI-I being intermediately formed from the amino nitrogen). By the presence of the ammonium ions, a basis is given for later formation of complex compounds.
In the next step, the double salts of trivalent rare earth and zinc are added to the acidic hydrolysate, while heating in the presence of the catalyst sodium peroxide. The complexes formed in analogy to the preparation of glycine-copper are precipitated in the cold at the isoelectric point in the neutral range with sodium hydroxide solution, and subsequently washed with 77 percent ethanol, and dried.
The carbonates of cerium and praseodymium and the sulfate of zinc proved to be especially suitable for reasons of easy handling and good yields.
In the following, the invention is more fully described by two examples which are given by way of illustration and not of limitation.
EXAMPLE 1 532.4 g of l-aspartic acid in 500 cc of distilled water and 600 cc of 37 percent HCl were hydrolysed with simultaneous conversion of the amino nitrogen into an ammonium salt. Thereafter, 550.37 g cerium carbonate and 161.44 g zinc sulfate were added, and the mixture heated to 40C, after addition of 0.1 g sodium peroxide as catalyst.
The so obtained solution was cooled to 30C after filtration from impurities in the cerium carbonate, if any; then 15 cc of 20 percent sodium hydroxide solution were added at room temperature. The precipitate which formed was separated by filtration and washed with 77 percent alcohol. Washing was repeated three times.
The residue obtained was dried at 40C in an oven; it is the cerium/zinc/aspartate complex. The yield amounted to about 850 g, the crystalline mass having a melting point of 243.5C and a molecular weight of 994.21.
EXAMPLE 2 The process was carried out as described in Example 1. However, instead of using cerium, praseodymium was used while the starting material was again 1- aspartic acid.
While the invention has been illustrated in two examples only, it should be understood that many modifications can be applied in the particulars without departing from the spirit of the invention and the scope of the following claims.
What is claimed is: 1. A complex compound of aspartic acid with a rare earth and zinc.
2. The. complex compound as recited in claim 1, wherein the rare earth is cerium.
3. The complex compound as recited in claim 1, wherein the rare earth is praseodymium.
4. A method of preparing a complex compound of aspartic acid with a rare earth and zinc, which comprises the steps of converting the amino nitrogen of aspartic acid into an ammonium salt;
adding a double salt to a trivalent rare earth and of zinc while using sodium peroxide as catalyst, thereby forming said complex salt; and
precipitating the complex compound with sodium hydroxide and crystallizing the compound by washing with alcohol.
5. The method as recited in claim 4, wherein step 2 is carried out with the carbonate of cerium or praseodymium and the sulfate of zinc.
6. The method as recited in claim 4 additionally comprising the step of drying the precipitate.
Claims (6)
1. A COMPLEX COMPOUND OF ASPARTIC ACID WITH A RARE EARTH AND ZINC.
2. The complex compound as recited in claim 1, wherein the rare earth is cerium.
3. The complex compound as recited in claim 1, wherein the rare earth is praseodymium.
4. A method of preparing a complex compound of aspartic acid with a rare earth and zinc, which comprises the steps of converting the amino nitrogen of aspartic acid into an ammonium salt; adding a double salt to a trivalent rare earth and of zinc while using sodium peroxide as catalyst, thereby forming said complex salt; and precipitating the complex compound with sodium hydroxide and crystallizing the compound by washing with alcohol.
5. The method as recited in claim 4, wherein step 2 is carried out with the carbonate of cerium or praseodymium and the sulfate of zinc.
6. The method as recited in claim 4 additionally comprising the step of drying the precipitate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US425060A US3899521A (en) | 1973-12-14 | 1973-12-14 | Complex compounds of aspartic acid with a rare earth metal and zinc |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US425060A US3899521A (en) | 1973-12-14 | 1973-12-14 | Complex compounds of aspartic acid with a rare earth metal and zinc |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3899521A true US3899521A (en) | 1975-08-12 |
Family
ID=23684975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US425060A Expired - Lifetime US3899521A (en) | 1973-12-14 | 1973-12-14 | Complex compounds of aspartic acid with a rare earth metal and zinc |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US3899521A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4195094A (en) * | 1977-12-23 | 1980-03-25 | Research Corporation | Zinc containing hypoglycemic agents |
| US5061815A (en) * | 1988-07-06 | 1991-10-29 | Zinpro Corporation | Metal lysine complexes and method for producing metal lysine complexes |
| WO2020022575A1 (en) * | 2017-11-28 | 2020-01-30 | (주)비티엔 | Amino acid mineral complex having immunopotentiating activity and composition for foods, pharmaceuticals, or feeds comprising same |
-
1973
- 1973-12-14 US US425060A patent/US3899521A/en not_active Expired - Lifetime
Non-Patent Citations (1)
| Title |
|---|
| Dreyer et al., Chem. Abs., Vol. 69, 100141q (1968). * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4195094A (en) * | 1977-12-23 | 1980-03-25 | Research Corporation | Zinc containing hypoglycemic agents |
| US5061815A (en) * | 1988-07-06 | 1991-10-29 | Zinpro Corporation | Metal lysine complexes and method for producing metal lysine complexes |
| WO2020022575A1 (en) * | 2017-11-28 | 2020-01-30 | (주)비티엔 | Amino acid mineral complex having immunopotentiating activity and composition for foods, pharmaceuticals, or feeds comprising same |
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